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Thursday, February 2, 2017

Asthma - from mouse to man

“The assessment of lung function endpoints
used in preclinical drug testing may hold the key to translation of drug
efficacy from mouse to man1.”

Bench-to-bedside

Mouse models have been and continue to be of
invaluable importance in asthma research, for the elucidation of key disease pathways
as well as in the assessment of potential therapies2. While therapeutic candidates showing promise
in murine models have not always translated into clinical successes, the story
behind the recent FDA-approved anti-IL-5 and anti-IL-13 therapies3,
previously deemed ineffective in general asthmatic populations, is a compelling
example of how a better understanding of both the underlying disease mechanisms
and the models resulted into “bench-to-bedside” achievements.

Mouse models of asthma

Asthma is a complex heterogeneous disease whose features
have not been completely depicted by any single mouse disease model. In preclinical (in vivo) research, careful considerations should be given to the
model employed, its phenotype, as well as the measured outcomes. Ideally, studies should include outcomes with
strong predictive or translational value such as lung function measurements. Respiratory function outcomes are often considered
as primary study endpoint in many clinical trials targeting asthma patients.
Therefore, relying on robust lung function measurements early on in the preclinical
validation and development of potential disease targets and therapeutic
candidates can, not only avoid misleading assessments, but also provide a
grounded approach to support the critical program decision-making process.

Lung function outcomes

Lung function outcomes provided by SCIREQ‘s flexiVent
and plethysmography methodologies aim to bridge the gap between mouse and man. Referenced in thousands of peer-reviewed scientific
publications and patents4, our scientific instruments permit accurate
and detailed measurements to complement and strengthen biochemistry or
immunology data. These measurements are conveniently
combined into a robust and comprehensive pulmonary assessment, collected via a computer-controlled
instrument that also maximizes reproducibility.

Future direction

Mouse models represent a highly valuable tool to study
the mechanisms involved in asthma and extrapolate scientific discoveries to
humans. The translatability of the
information provided will only be ensured in the future by the continuous
refinement of the models employed, as well as by a holistic approach combining
lung mechanics data to a comprehensive assessment of the model phenotype. This rigorous approach will hopefully help
identify target populations and lead to additional success stories in the
clinic, benefiting asthma patients worldwide.